AUXILIARY PARTIAL ORTHOTOPIC LIVER TRANSPLANTATION FOR FULMINANT HEPATIC FAILURE-PREDICTION AND PROMOTION OF DISEASED LIVER REGENERATION

<Experiment 1>本研究的目的是通过鹅膏毒素和内毒素的给药建立一种临床相关的暴发性肝功能衰竭（FHF）猪模型。猪门静脉内施用0. lmg/kg的α-鹅膏蕈碱+（n=9）。所有猪均在96 h内死亡，24 h时AST显著升高（9757±2167 IU/L）。此外，他们还表现出严重的代谢紊乱，如血清乳酸盐蓄积、低血糖、凝血障碍、血浆氨基酸失衡和高氨血症。死亡前颅内压显著升高至17.8±2.5 mm Hg。原位肝移植后FHF在这些猪中的复发证实了毒性是肝脏特异性的，并且移植肝不受影响。鹅膏蕈碱和LPS联合诱导的FHF猪模型将在开发人类FHF的新疗法中有很大用途。<Experiment 2>建立猪辅助性部分原位肝移植模型。从健康供体获得的左叶部分肝移植物在毒素施用和左叶切除后原位移植到受体中。所有猪均存活2周以上，术后1周肝活检可见病变肝再生。即使在一周时结扎左门静脉和左肝动脉后，猪随后仍以令人满意的肝功能存活。因此，我们建立了一个猪APOLT模型对抗我们新开发的方法使用鹅膏蕈碱和LPS诱导的FHF。患病的原生肝脏的再生似乎是在约一周内完成，其功能的完全恢复证实了移植肝的流入闭塞后的生存。

<Experiment 1> The purpose of this study was to develop a clinically relevant porcine model of fulminant hepatic failure (FHF) by means of administration of amatoxin and endotoxin. Pigs were intraportally administered 0.1 mg/kg of alpha-amanitin plus (n=9). All the pigs died within 96 hours with a significant increase in AST at 24 hr (9757±2167 IU/L). In addition, they demonstrated severe metabolic disorders such as serum lactate accumulation, hypoglycemia, coagulopathy, plasma amino acid imbalance, and hyperammonemia. Intracranial pressure significantly increased to 17.8±2.5 mm Hg immediately before death. Reversal of FHF in these pigs following orthotopic liver transplantation confirmed that the toxicity is liver-specific and that the graft liver is unaffected. This porcine model of FHF induced by a combination of amanitin and LPS will be of much use in the development of new therapies for human FHF.<Experiment 2> A porcine auxiliary partial orthotopic liver transplantation (APOLT) model for FHF was developed in the next study. A left lobe partial liver graft procured from a healthy donor was transplanted in the recipient in the orthotopic position after the toxin administration and left lobectomy. All the pigs survived more than 2 weeks after APOLT.Liver biopsy specimens one week after APOLT revealed regeneration of the diseased native liver. Even after the ligation of the left portal vein and left hepatic artery at one week, pigs subsequently survived with satisfactory liver function. Thus, we have established a porcine APOLT model against FHF induced by our newly developed method using amanitin and LPS.In this model, blood supply to the grafts was sufficient without portal diversion. Regeneration of the diseased native liver appeared to be accomplished in about one week, and full restoration of its function was confirmed by the survival after inflow occlusion of the graft liver.